Major Risk Factor Research Articles

Emerging Role of Environmental Epitranscriptomics and RNA Modifications in Parkinson's Disease.

Environmental risk factors and gene-environment interactions play a critical role in Parkinson's disease (PD). However, the relatively large contribution of environmental risk factors in the overwhelming majority of PD cases has been widely neglected in the field. A "PD prevention agenda" proposed in this journal laid out a set of research priorities focused on preventing PD through modification of environmental risk factors. This agenda includes a call for preclinical studies to employ new high-throughput methods for analyzing transcriptomics and epigenomics to provide a deeper understanding of the effects of exposures linked to PD. Here, we focus on epitranscriptomics as a novel area of research with the potential to add to our understanding of the interplay between genes and environmental exposures in PD. Both epigenetics and epitranscriptomics have been recognized as potential mediators of the complex relationship between genes, environment, and disease. Multiple studies have identified epigenetic alterations, such as DNA methylation, associated with PD and PD-related exposures in human studies and preclinical models. In addition, recent technological advancements have made it possible to study epitranscriptomic RNA modifications, such as RNA N6-methyladenosine (m6A), and a handful of recent studies have begun to explore epitranscriptomics in PD-relevant exposure models. Continued exploration of epitranscriptomic mechanisms in environmentally relevant PD models offers the opportunity to identify biomarkers, pre-degenerative changes that precede symptom onset, and potential mitigation strategies for disease prevention and treatment.

A review on comparative study of effectiveness of pregabalin and carbamazepine in painful diabetic peripheral neuropathy using mc gill's pain questionnaire

Diabetic neuropathy is a unique degenerative disorder of the peripheral nervous system that preferentially targets sensory axons and autonomic axons. The loss of sensory function that begins distally in the lower extremities is known as Diabetic neuropathy. It is characterized by burning pain, paresthesias and numbness in stocking glove pattern that progress proximally from the feet and hands. Diabetic neuropathy is a highly prevalent condition that substantially affects patients by increasing falls causing pain and reducing quality of life. The major risk factors for diabetic neuropathy is hyperglycemia. In addition to poor glycemic control, more-severe symptoms of diabetic neuropathy are associated with advanced age, hypertension, the duration of diabetes, dyslipidemia, smoking and heavy alcohol intake. Diabetic neuropathy is a major cause for disability of feet and hands globally. Anti-convulsants like pregabalin and carbamazepine are the medications used in the treatment of painful diabetic neuropathy.

Awareness of Hypertension, Hypercholesterolemia, and Diabetes Mellitus and Associated Characteristics in Russian Adults.

Russia has higher cardiovascular disease (CVD) mortality compared to other European countries. The major CVD risk factors are age, male sex, and three conditions, namely hypertension, hypercholesterolemia, and diabetes mellitus (DM). This study aimed to assess awareness of these three conditions among Russian adults (N = 3803) and the associated socio-demographic, lifestyle, and health characteristics. We used cross-sectional data from a randomly drawn population-based sample of Russians aged 35-69 years, who participated in the Know Your Heart (KYH) study conducted in Arkhangelsk and Novosibirsk between 2015-2018. Participants' self-reported awareness of hypertension, hypercholesterolemia, and DM was assessed against the measures at the KYH health check (blood pressure, cholesterol, HbA1c and/or use of medication for each condition). Prevalence estimates for the awareness were age- and sex-standardized to the Standard European Population. Socio-demographic, lifestyle, and health-related correlates of the awareness were investigated using logistic regression modelling. Among participants with hypertension (N = 2206), hypercholesterolemia (N = 3171), and DM (N = 329) recorded at a health check, 79%, 45%, and 61% self-reported these conditions, respectively. Higher awareness of hypercholesterolemia and hypertension was associated with older age, female sex, nonsmoking status, obesity, and history of CVD diagnoses. Low household income and history of CVD diagnoses were associated with being aware of DM. The awareness rates of hypertension were relatively high, whereas awareness rates of hypercholesterolemia and DM were relatively low. CVD prevention and early intervention could be improved in Russia through increasing the awareness of the risk factors.

Abstract 3774: Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma

Abstract Introduction and Objectives: The incidence of hepatocellular carcinoma (HCC) has almost tripled since the early 1980s in the United States where it is the fastest rising cause of cancer-related deaths. Advanced liver fibrosis and cirrhosis are ones of major risk factors for HCC. The recent evidence demonstrates that successfully treating the cause of early to moderate hepatic fibrosis may reverse most. For this reason, detecting hepatic fibrosis in an early stage is crucial. Liver biopsy is currently the gold standard for the assessment of hepatic fibrosis in clinical practice. Thus, there is an urgent clinical need for the development of non-invasive blood-based tests because of its ease of obtaining biological material. Previously, we developed FibraChek™, non-invasive blood-based tests. In this study, we tested the performance of FibraChek™ on detecting hepatic fibrosis and HCC in the US. Methods: The performance of FibraChek™ was evaluated in a single-institutional cohort of 14 prospectively collected subjects presenting for chronic liver disease (NAFLD/NASH) patients with hepatic fibrosis, 19 prospectively collected subjects diagnosed with HCC, and 12 prospectively collected controls from the US. The algorithm uses weighted value of the 5 biomarkers: AST, ALT, Platelet, Taurocholic Acid (TCA) & Tyrosine plus age to derive a risk score. The ability of the test to identify patients harboring hepatic fibrosis or HCC was assessed. Hepatic fibrosis status was confirmed by tissue biopsy or definitive surgery. Diagnostic performance was assessed using AUC. Results: FibraChek™ provided an AUC of 0.923 with an overall sensitivity of 93.9%, specificity of 81.8%, NPV 91.2% and PPV 81.8%. Interestingly, risk scores in HCC cohort indicated higher than those in patients with hepatic fibrosis. Thus, FibraChek™ may be also able to use for HCC detection. Conclusions: Serum levels of a biomarker panel enabled the accurate discrimination of hepatic fibrosis and controls. The FibraChek™ test can achieve the easy, efficient, and accurate detection of hepatic fibrosis and HCC in a non-invasive patient setting. Citation Format: Sunao Tanaka, Guoxiang Xie, Hideki Furuya, Wei Jia, Charles J. Rosser. Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3774.

Prevalence and Associated Risk Factors of Tuberculosis among Smear positive Contact Individuals in Port Sudan

Background: Tuberculosis is a necrotizing granulomatous multisystem infectious disease that caused by mycobacterium, mainly mycobacterium tuberculosis, It is a serious global health problem that represent the commonest infectious cause of death. Many risk factors contribute in spread of tuberculosis, these factors include environmental factors, host factors and factors related to organism. Contact with smear positive patients is a major risk factors as every infectious patient can transmit the organism to ten to fifteen persons; therefore, contact tracing being an important element in DOTS (Direct Observed Therapy Strategy), because early detection and early management of cases prevent complication and improve the outcome. Objectives: This study aims to determine the prevalence and assess risk factors of tuberculosis among TB smear positive contact whose registered in Port Sudan chest hospital TBMU center during third and fourth quarters; June to December 2023. Methodology: This is a descriptive cross sectional community base study, Port Sudan, eastern Sudan, from June 2023 to December 2023. Result: The study shows that prevalence of tuberculosis among smear positive contact individual is 4.6%s. And it shows other associated risk factors has a role in spread of the disease. Conclusion: The prevalence of tuberculosis among smear positive contact individuals in Port Sudan is low comparing to literature and other studies due to strong tuberculosis program and stigma also play a role in this reduction. Tuberculosis spread more among female and elder contact as the spend more time in the home. And immunosuppression, poor ventilation and crowded household play an essential role in spread of tuberculosis.

Effect of Perioperative Allogeneic Blood Transfusion in Causing Surgical Site Infection in Elective Gastrointestinal Surgeries: A Comparative Study among the Pediatric Population in A Tertiary Care Hospital of Bangladesh

Background: Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing elective gastrointestinal surgery. Objective: To find out whether perioperative allogeneic blood transfusion is a significant risk factor for surgical site infection in children undergoing elective gastrointestinal surgery. Methods: This prospective observational study was carried out at the Department of Pediatric Surgery in Dhaka Medical College Hospital, Dhaka, from January, 2021, to June, 2022, for a period of 18 months. According to CDC standards, patients who underwent elective gastrointestinal surgical procedure or clean-contaminated surgical wound (class II) were chosen as the study population. Total 256 patients were divided into two groups according to the blood transfusion as transfused and non-transfused group. Preoperative and postoperative day 1 CBC were done to observe the lymphocyte count. Blood transfusions were recorded during the perioperative period. After surgery, patients were followed up to check for surgical site infection and anastomotic leakage. Pus or wound swab for C/S was done in all the patients who developed SSI. The duration of the hospital stay after surgery was also noted. Results: Most of the study subjects in both the groups were ≤5 years(p=0.095). Males were predominant than females in both groups (p=0.014). Infection was found significantly higher among the transfused group (34.6%) than non-transfused group (14.6%) (p=0.001). In both the groups common infection was superficial SSI (12.0% in transfused group and 6.5% in non-transfused group). Among the infections, bacterial growth was 39.1% in Group A and 38.9% in Group B (p>0.786). Postoperative duration of hospital stay was 10.56 ± 4.05 days and 8.47 ± 2.67 days in Group A and Group B respectively (p<0.001). Mean lymphocyte count in Group A and group B was (2353.9±1647.7 vs 3792.5±1455.9; p<0.001). Conclusion: Allogeneic blood ........

Pulmonary edema in a young male with severe uncontrolled cardiovascular risk factors and pan-vascular atherosclerosis: a case report.

Cardiovascular risk factors are the cause of atherosclerotic disease, which can involve all the elastic and muscolo-elastic arteries. The etiopathogenesis of atherosclerosis is multifactorial since genetics, lifestyle, and comorbidities can be simultaneously involved. Clinical manifestations can be heterogeneous and include myocardial infarction, stroke, aortic aneurysms, renal artery stenosis, renal insufficiency, peripheral artery disease, etc. Currently, 70% of clinical events cannot be prevented with available drug therapy, statins included, and at least 10% of coronary events occur in apparently healthy individuals in the absence of major traditional risk factors. The case of a young male with a history of coronary artery disease and multiple atherosclerotic risk factors not properly treated who was admitted to the emergency department for pulmonary edema and high blood pressure is presented. During the diagnostic workup, a dramatic atherosclerotic involvement of all arterial trees emerged. Moreover, the patient presented with thrombosis of the right subclavian artery, which was treated with a heparin infusion and later complicated by cerebral hemorrhage with residual hemiplegia.

Sex-specific structural and functional cardiac remodeling during healthy aging assessed by cardiovascular magnetic resonance.

Aging as a major non-modifiable cardiac risk factor challenges future cardiovascular medicine and economic demands, which requires further assessments addressing physiological age-associated cardiac changes. Using cardiovascular magnetic resonance (CMR), this study aims to characterize sex-specific ventricular adaptations during healthy aging. The population included healthy volunteers who underwent CMR at 1.5 or 3 Tesla scanners applying cine-imaging with a short-axis coverage of the left (LV) and right (RV) ventricle. The cohort was divided by sex (female and male) and age (subgroups in years): 1 (19-29), 2 (30-39), 3 (40-49), and 4 (≥50). Cardiac adaptations were quantitatively assessed by CMR indices. After the exclusion of missing or poor-quality CMR datasets or diagnosed disease, 140 of 203 volunteers were part of the final analysis. Women generally had smaller ventricular dimensions and LV mass, but higher biventricular systolic function. There was a significant age-associated decrease in ventricular dimensions as well as a significant increase in LV mass-to-volume ratio (LV-MVR, concentricity) in both sexes (LV-MVR in g/ml: age group 1 vs. 4: females 0.50 vs. 0.57, p=0.016, males 0.56 vs. 0.67, p=0.024). LV stroke volume index decreased significantly with age in both sexes, but stronger for men than for women (in ml/m2: agegroup 1 vs. 4: females 51.76 vs. 41.94, p<0.001, males 55.31 vs. 40.78, p<0.001). Ventricular proportions (RV-to-LV-volume ratio) were constant between the age groups in both sexes. In both sexes, healthy aging was associated with an increase in concentricity and a decline in ventricular dimensions. Furthermore, relevant age-related sex differences in systolic LV performance were observed.

Young people's alcohol use in and around water: A scoping review of the literature.

The surrounding social and commercial context, including alcohol advertising, heavily influences alcohol consumption. Alcohol use is a major risk factor for both fatal and non-fatal drowning, particularly for young people. We conducted a scoping review to explore the peer-reviewed literature on the use of alcohol by young people (aged 15-34 years) in the context of aquatic environments. Five electronic academic databases were searched for English-language studies conducted in high-income countries and published in the last 15 years (since 2008). The MetaQAT framework was used to assess methodological quality of included studies. The review included a total of 24 studies, including those addressing the prevalence of and/or risk factors for alcohol use in aquatic environments among young people (n = 13); the epidemiology of alcohol-related unintentional drowning in young people (n = 9); and interventions to reduce alcohol-related harm around water (n = 3). Findings suggest that young people commonly consume alcohol around water, particularly young men. We found multiple influences on this behaviour, including the perception of risk, location of aquatic activity and presence of others, particularly peers. Understanding the literature addressing alcohol use around water among young people will assist in identifying and setting priorities for drowning prevention, including the need to mitigate the effects of alcohol advertising which promotes drinking in and around water. There is a clear imperative to address the use of alcohol by young people in aquatic environments. These findings have key implications for public health policy, advocacy and practice.

Left ventricular hypertrophy and left atrial diameter are associated with mortality risk in haemodialysis patients: a retrospective cohort study.

Cardiovascular death is the main cause of death in patients with end-stage kidney disease (ESKD). Left ventricular hypertrophy (LVH) and left atrial diameter (LAD) enlargement are frequent cardiac alterations in patients with ESKD and are major risk factors for cardiovascular events. However, it remains unclear whether there is an association between combined LAD or LVH and all-cause or cardiovascular mortality in this population. A single-centre, retrospective cohort study including 576 haemodialysis (HD) patients was conducted. Patients were evaluated by cardiac ultrasound, and the study cohort was divided into four groups according to LAD and LVH status: low LAD and non-LVH; low LAD and LVH; high LAD and non-LVH; and high LAD and LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyse all-cause and cardiovascular mortality after multivariate adjustment. LAD was associated with an increased risk of all-cause mortality (HR 2.371, 1.602-3.509; p < 0.001). No significant differences were found between LVH and the risk of all-cause mortality. Patients with high LAD and LVH had significantly greater all-cause and cardiovascular mortality than did those with low LAD and non-LVH after adjustments for numerous potential confounders (HR 3.080, 1.608-5.899; p = 0.001) (HR 4.059, 1.753-9.397; p = 0.001). Among maintenance haemodialysis (MHD) patients, LAD was more strongly associated with mortality than was LVH. A high LAD and LVH are associated with a greater risk of mortality. Our results emphasize that the occurrence of LAD and LVH in combination provides information that may be helpful in stratifying the risk of MHD patients.

Healthy Aging in Menopause: Prevention of Cognitive Decline, Depression and Dementia through Physical Exercise

The aging of the global population is a significant and complex phenomenon with far-reaching implications for healthcare systems and society. By 2030, it is projected that the number of individuals over the age of 65 will increase by nearly 1 billion, largely due to advancements in healthcare and improvements in quality of life. Aging is a multifaceted process that encompasses a wide array of changes, spanning from the cellular level to the intricate physiological systems of the human body. At the central nervous system level, aging represents a major risk factor for conditions such as depression and cognitive impairment, which are likely linked to neuroinflammatory processes and can potentially lead to more severe dementias, including Alzheimer’s disease (AD). The higher prevalence of AD in women compared to men has led to speculation that the onset of menopause and associated phenomena, particularly the decline in estrogen levels, may play a role in the development of the disease. Furthermore, research has shown that physical exercise confers both physical and mental health benefits to older adults, with women potentially experiencing the greatest advantages. Understanding the multifaceted nature of aging and its implications for health will ensure that older adults receive the support and care essential for maintaining their health and quality of life.

Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use Among Adults - United States, 2017-2021.

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke. It increases with age and is highest among non-Hispanic Black or African American persons, men, persons aged ≥65 years, those of lower socioeconomic status, and those who live in the southern United States. Hypertension affects approximately one half of U.S. adults, and approximately one quarter of those persons have their blood pressure under control. Reducing population-level hypertension prevalence and improving control is a national priority. In 2017, updated guidelines for high blood pressure in adults recommended lowering the blood pressure threshold for diagnosis of hypertension. Analysis of data from the Behavioral Risk Factor Surveillance System found that age-standardized, self-reported diagnosed hypertension was approximately 30% during 2017-2021, with persistent differences by age, sex, race and ethnicity, level of education, and state of residence. During this period, the age-standardized prevalence of antihypertensive medication use among persons with hypertension increased by 3.1 percentage points, from 59.8% to 62.9% (p<0.001). Increases in antihypertensive medication use were observed in most sociodemographic groups and in many states. Assessing current trends in hypertension diagnosis and treatment can help guide the development of policies and implementation of interventions to reduce this important risk factor for cardiovascular disease and can aid in addressing health disparities.

Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia.

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly increasing in the US, driven by its expanded approval for weight management in addition to hyperglycemia management in patients with type 2 diabetes. The perioperative safety of these medications, particularly with aspiration risk under anesthesia, is uncertain. To assess the association between GLP-1 RA use and prevalence of increased residual gastric content (RGC), a major risk factor for aspiration under anesthesia, using gastric ultrasonography. This cross-sectional study prospectively enrolled patients from a large, tertiary, university-affiliated hospital from June 6 through July 12, 2023. Participants followed preprocedural fasting guidelines before an elective procedure under anesthesia. Patients with altered gastric anatomy (eg, from previous gastric surgery), pregnancy, recent trauma (<1 month), or an inability to lie in the right lateral decubitus position for gastric ultrasonography were excluded. Use of a once-weekly GLP-1 RA. The primary outcome was the presence of increased RGC, defined by the presence of solids, thick liquids, or more than 1.5 mL/kg of clear liquids on gastric ultrasonography. Analysis was adjusted for confounders using augmented inverse probability of treatment weighting, a propensity score-based technique. Secondarily, the association between the duration of drug interruption and the prevalence of increased RGC was explored. Among the 124 participants (median age, 56 years [IQR, 46-65 years]; 75 [60%] female), the prevalence of increased RGC was 56% (35 of 62) in patients with GLP-1 RA use (exposure group) compared with 19% (12 of 62) in patients who were not taking a GLP-1 RA drug (control group). After adjustment for confounding, GLP-1 RA use was associated with a 30.5% (95% CI, 9.9%-51.2%) higher prevalence of increased RGC (adjusted prevalence ratio, 2.48; 95% CI, 1.23-4.97). There was no association between the duration of GLP-1 RA interruption and the prevalence of increased RGC (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14). Use of a GLP-1 RA was independently associated with increased RGC on preprocedural gastric ultrasonography. The findings suggest that the preprocedural fasting duration suggested by current guidelines may be inadequate in this group of patients at increased risk of aspiration under anesthesia.

Protective effect of SERCA2a-SUMOylation by SUMO-1 on diabetes-induced atherosclerosis and aortic vascular injury.

Diabetes is a major risk factor for cardiovascular disease. However, the exact mechanism by which diabetes contributes to vascular damage is not fully understood. The aim of this study was to investigate the role of SUMO-1 mediated SERCA2a SUMOylation in the development of atherosclerotic vascular injury associated with diabetes mellitus.ApoE-/- mice were treated with streptozotocin (STZ) injection combined with high-fat feeding to simulate diabetic atherosclerosis and vascular injury. Human aortic vascular smooth muscle cells (HAVSMCs) were treated with high glucose (HG, 33.3 mM) and palmitic acid (PA, 200 µM) for 24h to mimic a model of diabetes-induced vascular injury in vitro. Aortic vascular function, phenotypic conversion, migration, proliferation, intracellular Ca2+ concentration, the levels of small ubiquitin-like modifier type 1 (SUMO1), SERCA2a and SUMOylated SERCA2a were detected.Diabetes-induced atherosclerotic mice presented obvious atherosclerotic plaques and vascular injury, companied by significantly lower levels of SUMO1 and SERCA2a in aorta. HG and PA treatment in HAVSMCs reduced the expressions of SUMO1, SERCA2a and SUMOylated SERCA2a, facilitated the HAVSMCs phenotypic transformation, proliferation and migration, attenuated the Ca2+ transport, and increased the resting intracellular Ca2+ concentration. We also confirmed that SUMO1 directly bound to SERCA2a in HAVSMCs. Overexpression of SUMO1 restored the function and phenotypic contractile ability of HAVSMCs by upregulating SERCA2a SUMOylation, thereby alleviating HG and PA-induced vascular injury.These observations suggest an essential role of SUMO1 to protect diabetes-induced atherosclerosis and aortic vascular injury by the regulation of SERCA2a-SUMOylation and calcium homeostasis.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Chronic household air pollution and exposure patterns among Himalayan nomads.

Household air pollution (HAP) is a major risk factor of non-communicable diseases, causing millions of premature deaths each year in developing nations. Populations living at high altitudes are particularly vulnerable to HAP and associated health outcomes. This study aims to explore the relationships between activity patterns, HAP, and an HAP biomarker among 100 Himalayan nomadic households during both cooking and heating-only periods. Household CO was monitored in 100 rural homes in Qinghai, China, at 3500 m on the Himalayan Plateau among Himalayan nomads. Carboxyhemoglobin (COHb) was used as a biomarker to assess exposure among 100 male and 100 female heads of household. Linear mixed-effects models were used to explore the relationship between COHb and activity patterns. Cooking periods were associated with 7 times higher household CO concentrations compared with heating periods (94 ± 56 ppm and 13 ± 11 ppm, respectively). Over the three-day biomarker-monitoring period in each house, 99% of subjects had at least one COHb measurement exceeding the WHO safety level of 2%. Cooking was associated with a 32% increase in COHb (p < 0.001). This study on household air pollution (HAP) in high-altitude regions provides important insights into the exposure patterns of nomadic households in Qinghai, China. The study found that cooking is the primary factor influencing acute carbon monoxide (CO) exposure among women, while heating alone is sufficient to elevate CO exposure above WHO guidelines. The results suggest that cooking-only interventions have the potential to reduce HAP exposure among women, but solutions for both cooking and heating may be required to reduce COHb to below WHO guidelines. This study's findings may inform future interventions for fuel and stove selection to reduce HAP and exposure among other populations.

Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective

AbstractThe coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate.

(172) Managing Proximal Perforation of Inflatable Penile Prosthesis in Pelvic Trauma

Abstract Introduction Corporal perforation is a complication that occurs secondary to misdirected or over-aggressive dilation or weakened tunica albuginea. One major risk factor is corporal fibrosis, as the corpora is more difficult to dilate, and sharp dissection or counter-incisions may be required. Fibrosis is most commonly observed in patients with history of infection, priapism, Peyronie’s disease, or multiple revision surgeries. In the setting of pelvic trauma, normal anatomical landmarks can be altered leading to proximal perforation during dilation. Proximal corporal perforation first manifests as unequal corporal measurements intraoperatively or palpable malposition of the cylinder into the perineum. Objective Herein we discuss the case of a 24-year-old male with erectile dysfunction secondary to pelvic trauma who presents one year postoperatively with malposition of his right cylinder due to proximal migration from altered pelvic anatomy. We aim to describe our surgical techniques that can be utilized to correct proximal perforation. Methods Physical exam and preoperative imaging revealed grossly malpositioned right prosthetic cylinder. We utilized the prior transverse penoscrotal incision to deliver the scrotal pump from the surgical capsule. Given normal appearance of reservoir on imaging and duration from initial placement, only the scrotal pump and cylinders were exchanged. Bilateral cylinders were explanted through vertical corporotomies. Proximal measurements of 20cm on the left and 24cm on the right were consistent with corporal perforation. The Windsock procedure was performed by placing a 2–0 PDS suture from out to in through the tunica albuginea, through the right rear-tip extender, then in to out back through the albuginea of corporotomy. After copious irrigation of corporal space, new cylinders were placed using the modified rear tip extender. A new scrotal pump was placed in anterior dependent position. The device cycled properly in symmetric position bilaterally before all tissue layers were closed. Results The patient was observed overnight and discharged on post-operative day 1 after passing void trial. He was noted to be doing well at his post-operative clinic visit 6 weeks later and has been cleared for sexual activity. Conclusions We describe a patient with challenging anatomy due to extensive pelvic fracture leading to corporal perforation and proximal migration of a prosthetic cylinder. Due to lack of a normal pubic tubercle, we performed the Windsock sling procedure to provide posterior support of the right cylinder to prevent future proximal migration. An alternate approach is to secure the prosthesis tubing via sutures to the corporotomies is also presented. A critical intraoperative maneuver is evaluating for equal dilator depth alignment to recognize proximal perforation. These techniques can be applicable to other patients with altered anatomy secondary or in the setting of proximal corporal perforation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.

Perinatal risk factors associated with acute kidney injury severity and duration among infants born extremely preterm.

We evaluated time-varying perinatal risk factors associated with early (≤7 post-natal days) and late (>7 post-natal days) severe acute kidney injury (AKI) occurrence and duration. A secondary analysis of Preterm Erythropoietin Neuroprotection Trial data. We defined severe AKI (stage 2 or 3) per neonatal modified Kidney Disease: Improving Global Outcomes criteria. Adjusted Cox proportional hazards models were conducted with exposures occurring at least 72 h before severe AKI. Adjusted negative binomial regression models were completed to evaluate risk factors for severe AKI duration. Of 923 participants, 2% had early severe AKI. In the adjusted model, gestational diabetes (adjusted HR (aHR) 5.4, 95% CI 1.1-25.8), non-steroidal anti-inflammatory drugs (NSAIDs) (aHR 3.2, 95% CI 1.0-9.8), and vancomycin (aHR 13.9, 95% CI 2.3-45.1) were associated with early severe AKI. Late severe AKI occurred in 22% of participants. Early severe AKI (aHR 2.5, 95% CI 1.1-5.4), sepsis (aHR 2.5, 95% CI 1.4-4.4), vasopressors (aHR 2.9, 95% CI 1.8-4.6), and diuretics (aHR 2.6, 95% CI 1.9-3.6) were associated with late severe AKI. Participants who had necrotizing enterocolitis or received NSAIDs had longer severe AKI duration. We identified major risk factors for severe AKI that can be the focus of future research. Time-dependent risk factors for severe acute kidney injury (AKI) and its duration are not well defined among infants born <28 weeks' gestation. Over 1 in 5 infants born <28 weeks' gestation experienced severe AKI, and this study identified several major time-dependent perinatal risk factors occurring within 72 h prior to severe AKI. This study can support efforts to develop risk stratification and clinical decision support to help mitigate modifiable risk factors to reduce severe AKI occurrence and duration.

Abstract B109: Uncovering novel vulnerabilities in ovarian cancer by studying cell death in neoplastic transformation

Abstract B109: Uncovering novel vulnerabilities in ovarian cancer by studying cell death in neoplastic transformation